The people with haemophilia who face the greatest challenges in terms of current therapy are those with high titre inhibitors. There are a very small number of bypassing agents which can be used to treat people with inhibitors and their half-life is very short. There are a number of new and novel bypassing agents now under development which should greatly change the therapeutic landscape and improve the quality of life and therapeutic options for people with inhibitors. One of the current bypassing agents which is routinely used is factor VIIa. This is an effective therapy but it has a half-life of two hours. A new factor VIIa is under development which is linked to albumin and this will give a four-fold half-life extension to just over eight hours. A new anti-thrombin product (ALN/AT3SC), which goes under the name of Fitusiran, is under development. Anti-thrombin is a naturally occurring anticoagulant which activates thrombin and in people without bleeding disorders prevents too much coagulation. Fitusiran is a product which seeks to inhibit the effect of anti-thrombin and therefore increase the amount of coagulation. The product has had positive interim phase one results in clinical trials as a subcutaneously administered product. It dramatically reduces the levels of anti-thrombin in the blood and therefore allows more clotting to occur. A concern with a product like this would be that you could actually see thromboembolic events or too much coagulation occurring. This has not been seen in the clinical trials to date. To date, the clinical trials have shown a significant decrease in the annual bleed rate which seems to be linked to the proportional decrease in the antithrombin levels. The phase three trials for this product are now starting and this product may be a therapeutic option in the future for the treatment of inhibitors in haemophilia A and haemophilia B.

July 2016